ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.2002C>A (p.Pro668Thr) (rs1801183)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000214945 SCV000233368 benign not specified 2016-06-29 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000214945 SCV000268912 benign not specified 2015-05-08 criteria provided, single submitter clinical testing p.Pro668Thr in exon 29 of COL3A1: This variant is not expected to have clinical significance it has been identified in 0.8% (129/16334) of South Asian chromosom es and 0.1% (71/66412) European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs1801183). This variant has been r eported in one adult with abdominal aortic aneurysm and a nephew with an intracr anial aneurysm; however, the variant was also identifed in two unaffected, elder ly brothers (Tromp 1993).
PreventionGenetics,PreventionGenetics RCV000214945 SCV000302029 likely benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000181092 SCV000319468 benign Cardiovascular phenotype 2015-09-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Illumina Clinical Services Laboratory,Illumina RCV000380172 SCV000425524 likely benign Ehlers-Danlos syndrome, type 4 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000380172 SCV000554715 benign Ehlers-Danlos syndrome, type 4 2017-11-07 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514205 SCV000609835 likely benign not provided 2017-08-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000514205 SCV000695362 benign not provided 2017-04-17 criteria provided, single submitter clinical testing Variant summary: The COL3A1 c.2002C>A (p.Pro668Thr) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution. 4/5 in silico tools predict a damaging outcome for this variant, although the change still may be tolerated. This variant was found in the large control datasets of ExAC and gnomAD at a frequency of 0.00174 and 0.001629 (210/120672 and 451/276924 chrs tested, respectively), predominantly in South Asian individuals, including 5 homozygotes. The observed frequencies exceed the estimated maximal expected allele frequency of a pathogenic COL3A1 variant (0.0000013), indicating that the variant is a benign polymorphism. The variant of interest has been reported in several affected individuals via publications, but has failed to segregate with the disease (Tromp, 1993). Lastly, it has been classified as Benign/Likely Benign by multiple clinical diagnostic laboratories/reputable databases. Taking together, the variant is classified as Benign.
Center for Human Genetics, Inc RCV000380172 SCV000781235 uncertain significance Ehlers-Danlos syndrome, type 4 2016-11-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000514205 SCV000883647 benign not provided 2018-04-13 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769568 SCV000900965 benign Thoracic aortic aneurysm and aortic dissection 2017-08-23 criteria provided, single submitter clinical testing
Color RCV000769568 SCV000910958 benign Thoracic aortic aneurysm and aortic dissection 2018-03-16 criteria provided, single submitter clinical testing

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